[Show abstract][Hide abstract] ABSTRACT: To examine the expression of N-methylpurine-DNA glycosylase (MPG) gene and protein in glioma samples with different WHO grades and its association with patients' survival.
Immunohistochemistry assay, quantitative real-time PCR and Western blot analysis were carried out to investigate the expression of MPG gene and protein in 128 glioma and 10 non-neoplastic brain tissues.
MPG gene expression level in glioma tissues was significantly higher than that in non-neoplastic brain tissues (P < 0.001). Immunohistochemistry also showed that MPG protein was over-expressed in glioma tissues, which was consistent with the resutls of Western blot analysis. Additionally, the expression levels of MPG gene and protein both increase from grade I to grade IV glioma according to the results of real-time PCR, immunohistochemistry and western blot analysis. Moreover, the survival rate of MPG-positive patients was significantly lower than that of MPG-negative patients (P < 0.001). We further confirmed that the over-expression of MPG was a significant and independent prognostic indicator in glioma by multivariate analysis (P < 0.001).
Our data showed the over-expression of MPG gene and protein in human gliomas, and also suggested for the first time that MPG be an unfavorable independent prognostic indicator for glioma patients.
Full-text · Article · Feb 2012 · BioMed Research International
[Show abstract][Hide abstract] ABSTRACT: Gliomas are the most common primary intracranial tumors. Understanding the molecular basis of gliomas' progression is required to develop more effective therapies. The Wnt/β-catenin signaling cascade is an important signal transduction pathway in human cancers. Although, overactivation of this pathway is a hallmark of several forms of cancer, little is known about its role in human gliomas. Here, we aimed to determine the clinical significance of Wnt/β-catenin pathway components in gliomas. Immunohistochemical staining was performed to detect the expression patterns of Wnt1, β-catenin and Cyclin D1 in the biopsies from 96 patients with primary gliomas. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. Cytoplasmic staining pattern of Wnt1, membranous, cytoplasmic and nuclear accumulation of β-catenin, and nuclear localization of Cyclin D1 were demonstrated by immunohistochemical staining. The Wnt1 expression significantly correlated with the expression of Cyclin D1 (P < 0.0001). The ratio of tumors with a cytoplasmic-nuclear pattern or a cytoplasmic pattern of β-catenin was significantly higher in Wnt1-positive (P < 0.01) and Cyclin D1-positive (P < 0.01) tumors than in Wnt1-negative and Cyclin D1-negative tumors, respectively. The protein expression levels of Wnt1, β-catenin and Cyclin D1 were all positively correlated with the Karnofsky performance scale (KPS) score and World Health Organization (WHO) grades of patients with gliomas. Furthermore, Wnt1, cytoplasmic-nuclear β-catenin and Cyclin D1 status were all the independent prognostic factors for glioma patients (P = 0.01, 0.007 and 0.005, respectively). These results provide convincing evidence that the Wnt/β-catenin pathway correlated closely with the progression of gliomas and might be a novel prognostic marker for this neoplasm.
No preview · Article · Jun 2011 · Clinical and Experimental Medicine
[Show abstract][Hide abstract] ABSTRACT: Bone morphogenetic protein-2 (BMP-2) is normally expressed in the embryo promoting the development of several organs. Aberrant expression of BMP-2 occurs in various tumors. However, a correlation between BMP-2 expression in human gliomas and patients' prognosis has not been reported. To address this question, this study was to investigate the BMP-2 expression pattern in human gliomas and to evaluate its prognostic relevance.
We analyzed the expression of the BMP-2 antigen in a series of 98 gliomas of various grade and histology by immunohistochemistry on paraffin-embedded sections. Then, the correlation of BMP-2 expression pattern with clinical-pathological features of patients and its prognostic relevance were determined.
Immunohistochemical analysis with anti-BMP-2 antibody revealed dense and spotty staining in the tumor cells and its expression levels became significantly higher as the gliomas' grade advanced (P < 0.001). The median survival of patients with intensively positive BMP-2 expression was significantly shorter than that with negative expression (318 vs. 1197 days, P < 0.0001). The Kaplan-Meier survival curves showed that the BMP-2 expression was not only a significant predictor of survival in high-grade gliomas (grade IV, P = 0.02), but also in lower-grade gliomas (grades II and III, P < 0.001).
These results indicate that BMP-2 is a highly sensitive marker for gliomas prognosis and suggest that the expression level of BMP-2 may be a potent tool for the clinical prognosis of gliomas patients.
Preview · Article · Oct 2009 · Japanese Journal of Clinical Oncology